The objective of the project is a greater understanding of the molecular micro-architecture of the vitreous. Specifically, the project is directed toward elucidation of the extent, stability and structure of chain-chain interactions in high molecular weight vitreous hyaluronic acid. Initial efforts will be devoted to the development of a model system for the study of intermolecular interactions in the absence of intramolecular chain segment associations. Highly purified defined molecular weight segments of hyaluronic acid will be isolated and studied under differing solvent conditions. The extent of chain-chain association and the conformational changes accompanying interaction will be investigated by a variety of biochemical and biophysical methods. Specific methodology planned includes chromotography, viscometry, enzyme reactivity, proton exchange kinetics, and spectroscopy. The role of hydrogen bonds and/or specific ion effects in stabilizing intermolecular association will be determined. The model system data and biophysical assay techniques developed will be extended to studies on high molecular weight purified hyaluronic acid and to native vitreous hyaluronic acid. For these latter cases, the investigation will determine the influence of concentration, molecular weight, and possible influence of other molecular species in the vitreous on hyaluronic acid chain-chain interactions leading to the formation of a network-like matrix.